Identification

Name
Lucanthone
Accession Number
DB04967
Type
Small Molecule
Groups
Investigational
Description

One of the schistosomicides, it has been replaced largely by hycanthone and more recently praziquantel. (From Martindale The Extrapharmacopoeia, 30th ed., p46). It is currently being tested as a radiation sensitizer.

Structure
Thumb
Synonyms
  • 1-((2-(Diethylamino)ethyl)amino)-4-methylthioxanthen-9-one
  • 1-{[2-(diethylamino)ethyl]amino}-4-methylthioxanthen-9-one
  • 1-diethylaminoethylethylamino-4-methyl-thioxanthenone
  • Lucanthone
  • Lucanthonum
  • Lucantona
Product Ingredients
IngredientUNIICASInChI Key
Lucanthone hydrochloride918K9N56QZ548-57-2LAOOXBLMIJHMFO-UHFFFAOYSA-N
International/Other Brands
Miracil D
Categories
UNII
FC6D57000M
CAS number
479-50-5
Weight
Average: 340.482
Monoisotopic: 340.16093409
Chemical Formula
C20H24N2OS
InChI Key
FBQPGGIHOFZRGH-UHFFFAOYSA-N
InChI
InChI=1S/C20H24N2OS/c1-4-22(5-2)13-12-21-16-11-10-14(3)20-18(16)19(23)15-8-6-7-9-17(15)24-20/h6-11,21H,4-5,12-13H2,1-3H3
IUPAC Name
1-{[2-(diethylamino)ethyl]amino}-4-methyl-9H-thioxanthen-9-one
SMILES
CCN(CC)CCNC1=C2C(=O)C3=CC=CC=C3SC2=C(C)C=C1

Pharmacology

Indication

Intended for use as a radiation sensitizer in the treatment of brain cancer.

Pharmacodynamics

Although lucanthone has structural and biochemical similarities to Actinomycin D, it has no hematological or gastro-intestinal toxicity at clinically tolerated doses. In trials, Lucanthone was found to be safe, practical and effective and was proposed for use in clinical protocols for the treatment of cancer. The specificity of lucanthone in combination with radiation for the treatment of brain tumors arises from the fact that lucanthone acts preferentially on cycling cells (most of the normal brain cells are non-cycling) and the fact that lucanthone crosses the blood brain barrier efficiently.

Mechanism of action

Recent data suggests that lucanthone inhibits post-radiation DNA repair in tumor cells. The ability of lucanthone to inhibit AP endonuclease and topoisomerase II probably account for the specific DNA repair inhibition in irradiated cells.

TargetActionsOrganism
ADNA topoisomerase 2-alpha
inhibitor
Human
ADNA-(apurinic or apyrimidinic site) lyase
inhibitor
Human
ADNA
intercalation
Human
ADNA topoisomerase 1
inhibitor
Human
Absorption

Orally available

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
  1. Luo M, Kelley MR: Inhibition of the human apurinic/apyrimidinic endonuclease (APE1) repair activity and sensitization of breast cancer cells to DNA alkylating agents with lucanthone. Anticancer Res. 2004 Jul-Aug;24(4):2127-34. [PubMed:15330152]
  2. Del Rowe JD, Bello J, Mitnick R, Sood B, Filippi C, Moran J, Freeman K, Mendez F, Bases R: Accelerated regression of brain metastases in patients receiving whole brain radiation and the topoisomerase II inhibitor, lucanthone. Int J Radiat Oncol Biol Phys. 1999 Jan 1;43(1):89-93. [PubMed:9989518]
External Links
Human Metabolome Database
HMDB0015607
KEGG Compound
C11715
PubChem Compound
10180
PubChem Substance
46507260
ChemSpider
9772
BindingDB
50030282
ChEBI
51052
ChEMBL
CHEMBL279014
Therapeutic Targets Database
DAP001003
PharmGKB
PA164748783
Wikipedia
Lucanthone

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2TerminatedTreatmentGlioblastoma Multiforme (GBM)1
2WithdrawnTreatmentLung Cancer Non-Small Cell Cancer (NSCLC) / Metastatic Brain Tumors1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00315 mg/mLALOGPS
logP4.72ALOGPS
logP5.02ChemAxon
logS-5ALOGPS
pKa (Strongest Acidic)18.84ChemAxon
pKa (Strongest Basic)8.69ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area32.34 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity106.01 m3·mol-1ChemAxon
Polarizability39.6 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9644
Blood Brain Barrier+0.9538
Caco-2 permeable+0.5555
P-glycoprotein substrateSubstrate0.8992
P-glycoprotein inhibitor IInhibitor0.62
P-glycoprotein inhibitor IINon-inhibitor0.7254
Renal organic cation transporterNon-inhibitor0.5391
CYP450 2C9 substrateNon-substrate0.6567
CYP450 2D6 substrateSubstrate0.545
CYP450 3A4 substrateSubstrate0.5259
CYP450 1A2 substrateInhibitor0.8476
CYP450 2C9 inhibitorNon-inhibitor0.8837
CYP450 2D6 inhibitorInhibitor0.704
CYP450 2C19 inhibitorNon-inhibitor0.7842
CYP450 3A4 inhibitorNon-inhibitor0.5884
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.6989
Ames testAMES toxic0.9107
CarcinogenicityNon-carcinogens0.761
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.5482 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.6183
hERG inhibition (predictor II)Inhibitor0.8499
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as thiochromenes. These are organosulfur compounds that are analogues to chromene, with the difference that a sulfur atom replaces the oxygen atom.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Thiochromenes
Sub Class
Not Available
Direct Parent
Thiochromenes
Alternative Parents
1-benzothiopyrans / Secondary alkylarylamines / Benzenoids / Vinylogous amides / Heteroaromatic compounds / Trialkylamines / Organopnictogen compounds / Organooxygen compounds / Organic oxides / Hydrocarbon derivatives
Substituents
Thiochromene / Benzothiopyran / 1-benzothiopyran / Secondary aliphatic/aromatic amine / Benzenoid / Heteroaromatic compound / Vinylogous amide / Tertiary aliphatic amine / Tertiary amine / Secondary amine
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
thioxanthenes (CHEBI:51052)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Ubiquitin binding
Specific Function
Control of topological states of DNA by transient breakage and subsequent rejoining of DNA strands. Topoisomerase II makes double-strand breaks. Essential during mitosis and meiosis for proper segr...
Gene Name
TOP2A
Uniprot ID
P11388
Uniprot Name
DNA topoisomerase 2-alpha
Molecular Weight
174383.88 Da
References
  1. Bases RE, Mendez F: Topoisomerase inhibition by lucanthone, an adjuvant in radiation therapy. Int J Radiat Oncol Biol Phys. 1997 Mar 15;37(5):1133-7. [PubMed:9169823]
  2. Dassonneville L, Bailly C: Stimulation of topoisomerase II-mediated DNA cleavage by an indazole analogue of lucanthone. Biochem Pharmacol. 1999 Oct 15;58(8):1307-12. [PubMed:10487533]
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Uracil dna n-glycosylase activity
Specific Function
Multifunctional protein that plays a central role in the cellular response to oxidative stress. The two major activities of APEX1 in DNA repair and redox regulation of transcriptional factors. Func...
Gene Name
APEX1
Uniprot ID
P27695
Uniprot Name
DNA-(apurinic or apyrimidinic site) lyase
Molecular Weight
35554.165 Da
References
  1. Luo M, Kelley MR: Inhibition of the human apurinic/apyrimidinic endonuclease (APE1) repair activity and sensitization of breast cancer cells to DNA alkylating agents with lucanthone. Anticancer Res. 2004 Jul-Aug;24(4):2127-34. [PubMed:15330152]
3. DNA
Kind
Nucleotide
Organism
Human
Pharmacological action
Yes
Actions
Intercalation
General Function:
Used for biological information storage.
Specific Function:
DNA contains the instructions needed for an organism to develop, survive and reproduce.
Molecular Weight:
2.15 x 1012 Da
References
  1. Milligan AJ, Metz JA, Leeper DB: The effect of lucanthone on sublethal radiation damage, in vivo. Int J Radiat Oncol Biol Phys. 1984 Dec;10(12):2309-13. [PubMed:6392224]
  2. Bailly C, Waring MJ: Preferential intercalation at AT sequences in DNA by lucanthone, hycanthone, and indazole analogs. A footprinting study. Biochemistry. 1993 Jun 15;32(23):5985-93. [PubMed:8389585]
  3. Dassonneville L, Bailly C: Stimulation of topoisomerase II-mediated DNA cleavage by an indazole analogue of lucanthone. Biochem Pharmacol. 1999 Oct 15;58(8):1307-12. [PubMed:10487533]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Poly(a) rna binding
Specific Function
Releases the supercoiling and torsional tension of DNA introduced during the DNA replication and transcription by transiently cleaving and rejoining one strand of the DNA duplex. Introduces a singl...
Gene Name
TOP1
Uniprot ID
P11387
Uniprot Name
DNA topoisomerase 1
Molecular Weight
90725.19 Da
References
  1. Bases RE, Mendez F: Topoisomerase inhibition by lucanthone, an adjuvant in radiation therapy. Int J Radiat Oncol Biol Phys. 1997 Mar 15;37(5):1133-7. [PubMed:9169823]
  2. Dassonneville L, Bailly C: Stimulation of topoisomerase II-mediated DNA cleavage by an indazole analogue of lucanthone. Biochem Pharmacol. 1999 Oct 15;58(8):1307-12. [PubMed:10487533]

Drug created on October 21, 2007 16:23 / Updated on November 02, 2018 08:42